Shown is a bioengineered blood vessel, manufactured by Humacyte, as doctors implant it in the arm of a volunteer undergoing dialysis. Credit: Duke University

Scientists have been working for decades to develop better ways to repair or replace blood vessels damaged by disease or trauma. And while they can claim some progress, they concede that many patients needing vascular care still face challenges: long wait times due to a shortage of donor vessels, painful procedures to take blood vessels from the patients’ own limbs, and failure of the synthetic vessels currently on the market to achieve the same outcomes as the patients’ own vessels.

Now, a group of researchers at Humacyte, a biotech company in North Carolina, have developed a different kind of replacement vessel that might have the potential to revolutionize the treatment of vascular disease. The vessel, which has already advanced through Phase II clinical trials, is bioengineered to look, feel, and function much like a human blood vessel, including in its capacity to be accepted by the body. Importantly, it could be stored for up to a year or more for future use—the first-ever bioengineered vessel with that capability. Scientists are now testing the experimental blood vessel in Phase III clinical trials (the last stage of testing before submission for FDA registration).

“We’re excited because it represents the first time that patients will have access to a life-like human blood vessel that’s essentially off-the-shelf,” said Shannon Dahl, Ph.D., a bioengineer and a co-founder of Humacyte. “If our clinical trials are successful, it could set the stage for vessels for coronary bypass on the heart or other engineered-tissue technologies, like artificial organs.”

NHLBI Small Business Program funding gives boost to life-like grafts to improve treatment

Humacyte is a women-founded small business that was launched in 2004 by Laura Niklason, M.D., Ph.D., Juliana Blum, Ph.D., and Dahl. The company now employs over 90 people.

Company-founder Niklason is currently Professor of Anesthesiology & Biomedical Engineering at Yale University. Prior to starting Humacyte, she received research funding from the National Heart, Lung, and Blood Institute (NHLBI) to develop the technology for engineering vascular grafts. The NHLBI has since supported the development of Humacyte’s replacement blood vessel product with funding from its Small Business Innovation Research (SBIR) program. In addition, the company has received an award from the NHLBI’s Vascular Interventions/Innovations and Therapeutic Advances (VITA) Program to advance the clinical development of its engineered vessels.

“We’re excited because it represents the first time that patients will have access to a life-like human blood vessel that’s essentially off-the-shelf. ”

— Shannon Dahl, Ph.D., bioengineer and a co-founder of Humacyte

Humacyte’s artificial blood vessel could be helpful in several critical care settings. For example, vascular grafts allow convenient and rapid access to the bloodstream of kidney disease patients to optimize dialysis, a mechanical process for cleaning the blood when the kidneys are failing.

Replacement vessels are also used routinely in coronary bypass surgery. Current artificial blood vessels have had only limited success in this situation due to risks of infection and clotting. Meanwhile, demand for a more reliable replacement vessel continues to grow because of increasing rates of diabetes and heart disease.

Humacyte’s bioengineered vessels are grown from smooth muscle cells derived from human tissue donors. These human cells are cultured in a bioreactor, a special chamber used to speed cell growth. The cells assemble around a tube-shaped polymer scaffold that degrades as the cells form the shape of a blood vessel.

The scientists eventually remove the cells from the cultured tissue, leaving behind mechanically strong tube-shaped tissue. Removal of these donor cells, researchers say, is what gives the vessel its key benefit: the ability to avoid rejection by the body’s immune system. But the bioengineered vessels have something else beneficial—they can also be stored for several months in refrigerated saline solution at the hospital so that they are ready for use in surgery when needed.

Early clinical studies that were partially funded by the SBIR program showed that the vessels were safe and well-tolerated when used for dialysis in a group of 60 patients with end-stage kidney disease. The vessels provided a way to reach the blood so that a dialysis machine could remove the waste normally processed by the kidney. The vessels functioned as expected during that year-long study. In addition, the researchers did not see evidence that the immune system was rejecting the vessel.

Perhaps the biggest test of the new technology, though, will be the Phase III clinical trials, which are currently underway. The first Phase III trial will enroll more than 350 patients undergoing dialysis to compare the effects of the new technology to synthetic polymer grafts currently used for dialysis access. Final results are expected in 2019, after which Humacyte will submit a request for FDA marketing approval. These bioengineered vessels could available to patients within three years, scientists say.

Besides their use in dialysis and heart disease, the investigators say that these bioengineered vessels could be used to treat victims of car accidents, gunshots, and other trauma situations that may involve damaged blood vessels.

More about the NHLBI SBIR and STTR programs

The NHLBI Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support research and development on the next generation of commercially promising technologies and products to prevent, diagnose, and treat heart, lung, blood, and sleep-related diseases and disorders. For more information on NHLBI’s small business programs, visit http://www.nhlbi.nih.gov/research/funding/sbir/about-program

Disclaimer

Reference to any specific commercial products, process, service, manufacturer, and/or company does not constitute an endorsement or recommendation by the National Heart, Lung, and Blood Institute (NHLBI), the NHLBI's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, or any other portion of the U.S. Government.